Diabetes
Maria G. Tanzi, PharmD
New evidence supporting the use of select oral and topical agents for the management of painful diabetic neuropathy is discussed in an updated guideline released in December 2021 by the American Academy of Neurology (AAN).
“Living with pain can greatly affect a person’s quality of life, so this guideline aims to help neurologists and other doctors provide the highest quality patient care based on the latest evidence,” said guideline author Brian C. Callaghan, MD, MS, of the University of Michigan and a Fellow of the AAN in a press release. “Painful diabetic neuropathy is very common, so people with diabetes who have nerve pain should discuss it with their doctor because treatment may help.”
Oral treatments
Based on an extensive review of the data, the AAN recommends that patients interested in receiving oral treatments be offered tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentinoids, and/or sodium channel blockers to reduce pain. These 4 classes of medications have evidence supporting their effects on pain reduction, with comparable effects.
This updated guideline takes into account the most recent evidence. The previous guideline on the management of painful diabetic neuropathy was released in 2011.
When selecting between drug classes, clinicians should consider concurrent comorbidities of patients. Patients with depression/anxiety may have a dual benefit with use of the TCAs and/or SNRIs, whereas those with a history of seizures may be better suited for the gabapentinoids and/or sodium channel blockers.
The potential adverse effects of these medications are also a key consideration for clinicians. For example, TCAs are associated with anticholinergic adverse effects and may not be as well tolerated in those with pre-existing urinary retention or constipation. Clinicians and patients should consider the potential for nausea, fatigue, and dizziness with SNRIs and sodium channel blockers, and peripheral edema as a potential adverse effect from the use of gabapentinoids.
Since valproic acid is potentially teratogenic, this medication should not be used in patients of childbearing age. The AAN also recommends that valproic acid not be used unless multiple other medications have already been tried but failed to provide relief because of the potential for serious adverse events.
The AAN guideline defines “treatment failure” as an effective dose of a treatment that has been tried for approximately 12 weeks without any clinically significant pain reduction or when adverse effects of the medication outweigh the benefits. When treatment fails a patient, the guideline authors recommended offering a trial from a different class. Also, for those experiencing a partial improvement, a trial from a different class can also be given to patients or combination therapy may be considered.
Topical, other options
Some patients may prefer topical or nonpharmacological treatment options for managing diabetic neuropathy, which AAN addresses in the new guideline. Although the evidence is limited, at least some data support the use of other interventions such as topical (e.g., capsaicin, glyceryl trinitrate spray, Citrullus colocynthis), nontraditional (Ginkgo biloba), or nonpharmacologic options (e.g., exercise, cognitive behavioral therapy, Tai Chi, mindfulness).
In the new guideline, the AAN also indicates that opioids, tramadol, or tapentadol should not be used for the treatment of diabetic neuropathy. These medications should be avoided because of the potential for long-term adverse consequences such as dependence, misuse/abuse, and overdose. If patients are receiving these agents, the AAN recommends that clinicians offer the option of safe tapering off these drugs and a discussion on alternative, nonopioid treatment strategies.
Educational pearls
Painful peripheral neuropathy is a common complication for patients with diabetes, especially for those who have long-standing disease and poor glycemic control.
Clinicians should assess patients with diabetes for this condition and how it impacts their quality of life. For patients who are starting a new treatment for neuropathic pain, clinicians should discuss that the treatment will likely reduce pain but won’t necessarily eliminate it.
Patients should also understand potential adverse effects with selected treatments, which should be reported to their provider. As there are many oral and topical treatments for diabetic peripheral neuropathy, treatment should be tailored to meet individual patient needs, with consideration given to cost, patient preference, comorbidities, and safety. ■